2,4-Difluorobenzoyl chloride → [4-(2,4-Diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]-(2,4-difluorophenyl)methanone

HRID 1015348Notes

Reaction equation

HRID 1015348 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][O:8][C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[C:11]([NH2:20])=[N:12][C:13]([NH2:19])=[N:14]3)[CH2:3][CH2:2]1.[F:21][C:22]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25]>>[NH2:19][C:13]1[N:12]=[C:11]([NH2:20])[C:10]2[C:15](=[CH:16][CH:17]=[CH:18][C:9]=2[O:8][CH2:7][CH:4]2[CH2:5][CH2:6][N:1]([C:24]([C:23]3[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:22]=3[F:21])=[O:25])[CH2:2][CH2:3]2)[N:14]=1

Participants

3

Reactant 2

HCID 5880812,4-Difluorobenzoyl chlorideHCID 575765655-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine

Product 1

HCID 25002760[4-(2,4-Diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]-(2,4-difluorophenyl)methanoneYield 71%

Procedure

The amidation of 5-(piperidin-4-ylmethoxy)quinazoline-2,4-diamine (50 mg; 0.18 mmol) was carried out using 2,4-difluorobenzoyl chloride (65 mg; 0.37 mmol) via Method AA to yield 108 mg. (71% yield). 1HNMR (400 MHz, DMSO-d6) δ 7.48 (m, 1H), 7.35 (m, 2H), 7.18 (m, 3H), 6.77 (d, J=8.0 Hz, 1H), 6.54 (d, J=8.0 Hz, 1H), 5.94 (br s, 2H), 4.53 (br d, J=13.2 Hz, 1H), 4.03 (d, J=6.0 Hz, 2H), 3.44 (m, 1H), 3.12 (t, J=12.8 Hz, 1H), 2.85 (m, 1H), 2.22 (m, 1H), 1.9 (d, J=12.4 Hz, 1H), 1.74 (d, J=12.4 Hz, 1H), 1.26 (m, 2H). MS m/z (ESI) 414 (M+H)+.

Workup

  1. customto yield 108 mg

Sources & evidence

ORD record
ord-8a4649f8326d4bd7a908f62b6d49d812
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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